Decreased expression of surfactant protein D mRNA in human lungs in fatal cases of H5N1 avian influenza

Abstract

Microarray analysis of gene expression profile of lungs from two fatal H5N1 influenza cases identified 3,435 genes with higher than twofold changes in mRNA levels as compared to those of normal lung. One thousand nineteen genes and 2,416 genes were up-regulated and down-regulated commonly, respectively. Gene ontology analysis identified several ontology terms with significant association with these genes, most of which are related to cellular metabolism and regulation of cellular process including apoptosis and chemotaxis. Pulmonary surfactant protein D (SP-D) was found to be down-regulated. Quantitative RT-PCR confirmed the levels of SP-D mRNA in the lungs infected with H5N1 to be lower than those of normal lungs and lungs from patients with acute respiratory distress syndrome. SP-D plays multiple roles in respiratory innate defense against various pathogens, regulation of inflammatory responses, and maintenance of alveolar integrity. Reduction of SP-D in H5N1 influenza may play important roles in the pathogenesis of the disease.

The Impact of Focused Gene Ontology Curation of Specific Mammalian Systems

“…As yet, we have found no evidence of unexpected cardiovascular and renal terms, being detected in term enrichment analyses. Recent microarray analysis, using GO, of vulvar carcinoma [30] and H5N1 influenza infected lungs [31] mostly identified enrichment of only general biological process terms, such as ‘ cell death ’, ‘ cell growth ’, ‘ cell communication ’ and ‘ cell-to-cell signaling ’. Although, the lung analysis also identified enrichment of more specific GO terms, such as ‘ viral reproduction ’, ‘ chemotaxis ’ and ‘ vesicle-mediated transport ’.…”

Soluble Host Defense Lectins in Innate Immunity to Influenza Virus

“…Microarray analysis and quantitative RT-PCR showed SP-D expression to be reduced in lungs from two fatal cases of H5N1 IAV infection when compared to healthy patients or patients with acute respiratory distress syndrome [130], although other studies noted no major changes in SP-D expression in the airways of H5N1-infected ferrets [131] or macaques [132]. In addition, 2 human H5N1 strains that were less glycosylated than recent seasonal H1N1 and H3N2 strains were also resistant to SP-D in vitro [58], consistent with the notion that SP-D-mediated defenses may be ineffective against H5N1 strains.…”

Serum surfactant protein D is associated with the prognosis in patients with chronic kidney disease

“…4 Circulating surfactant protein D (SP-D) is one of the mammalian collagenous lectins called collectins, 5 mainly found in the lung and secreted to the alveolar surface. 6 SP-D has been proved to be associated with many pulmonary diseases, such as acute respiratory distress syndrome and acute lung injury, 7 interstitial lung disease, 8 chronic obstructive pulmonary disease, 9 idiopathic pulmonary fibrosis, 10 H5N1 influenza 11 and respiratory syncytial virus bronchiolitis. 12 Recently, SP-D was also found to be present in endothelial and vascular smooth muscle cells (SMCs) of humans, and exerts an anti-inflammatory action in human coronary artery SMCs.…”